Since the discovery of RNA interference (RNAi), small interfering RNAs (siRNAs) have been exploited as a new potential therapeutic strategy [1]. Among promising applications of siRNA is down-regulation of drug resistance pathways developed in aggressive cancer cells, which enables targeted therapy of specific tumor types with poor prognosis. Combining such gene-targeting siRNA with anticancer agents through a co-delivery system can disarm the resistant cells to greatly improve the treatment efficacy of chemotherapy (chemosensitization) [2, 3]. From a clinical viewpoint, however, the development of siRNA therapeutics is limited by a lack of suitable nonviral delivery systems. Although many attempts have been made in similar ways applied to DNA delivery, they are not fully suited to the delivery of siRNA as it has different physicochemical features such as short chain length and rigid backbone structure compared to DNA [4, 5]. The typical mechanism for nanoscopic gene packaging has been primarily based on the electrostatic polycomplexation between polyanionic genes and complexing agents (cationic polymers or liposomes) [6]. In addition, Previous studies revealed that the electrostatic interaction between DNA and monocationic surfactants can produce organic-soluble complexes to make water-insoluble functional solids [7]. In these complexes, each anionic charge along the polyanionic DNA backbone undergoes monocomplexation with a cationic surfactant molecule. As a result, every single chain of DNA is surrounded with a number of surfactants by multiple monocomplexation and the overall charge neutralization induces solubility reversal to produce surfactant-jacketed hydrophobized DNA chains with organic solubility. However, the resulting polyplex/lipoplex systems in clinical applications have diverse problems, for example including need on a high molar ratio of cytotoxic cationic agent-to-siRNA necessary for complete complexation according to inefficient/loose packaging of short/rigid siRNA. Accordingly, there has been a demand on a siRNA/drug co-delivery system for clinical applications in an effective manner.
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.